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<title>
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Entry
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- #137550 - MELANOCYTIC NEVUS SYNDROME, CONGENITAL; CMNS
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- OMIM
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<span class="h4">#137550</span>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(MELANOCYTIC NEVUS SYNDROME, CONGENITAL) OR (NRAS OR HRAS)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=370&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/giant-congenital-melanocytic-nevus" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=626" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0111359" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/137550" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0111359" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 10291008, 1260467009<br />
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<strong>ORPHA:</strong> 626<br />
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<strong>DO:</strong> 0111359<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
|
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137550
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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MELANOCYTIC NEVUS SYNDROME, CONGENITAL; CMNS
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</span>
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</h3>
|
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</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
GIANT PIGMENTED HAIRY NEVUS; GPHN<br />
|
|
GIANT CONGENITAL PIGMENTED NEVUS<br />
|
|
PIGMENTED MOLES
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
NEVUS SPILUS, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
SPITZ NEVUS, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
</div>
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|
|
|
|
|
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|
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|
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|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/943?start=-3&limit=10&highlight=943">
|
|
1p13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Melanocytic nevus syndrome, congenital, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/137550"> 137550 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
NRAS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/164790"> 164790 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/29?start=-3&limit=10&highlight=29">
|
|
11p15.5
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Spitz nevus or nevus spilus, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/137550"> 137550 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
HRAS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/190020"> 190020 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/137550" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/137550" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/137550" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Somatic mutation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/124975008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">124975008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866227</a>, <a href="https://bioportal.bioontology.org/search?q=C0544886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0544886</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Wide forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Forehead,Broad-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Prominent forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837260</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011220</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011220</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=a2091161c29564b62e12b608022a4044" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Forehead,Prominent-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=a2091161c29564b62e12b608022a4044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Round face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000311" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000311</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000311" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000311</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ab9bbad3c428d627c2b454902c17fa0" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Face,Round-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ab9bbad3c428d627c2b454902c17fa0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Full cheeks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=85459d10e5df48479ec4a2ec6cfc0455" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Cheeks,Full-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=85459d10e5df48479ec4a2ec6cfc0455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Prominent premaxilla <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749369&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749369</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010759" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010759</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010759" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010759</a>]</span><br /> -
|
|
Long philtrum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1865014&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1865014</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Philtrum,Long-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Deep philtrum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839797&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839797</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002002</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002002</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=02d740f0400c0ba4b43a2532cfbf67e5" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Philtrum,Deep-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=02d740f0400c0ba4b43a2532cfbf67e5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Apparent hypertelorism <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4011555&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4011555</a>]</span><br /> -
|
|
Eyebrow abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4011556&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4011556</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000534" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000534</a>]</span><br /> -
|
|
Periorbital fullness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4760994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4760994</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000629</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Nose </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Narrow nasal ridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837761&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837761</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000418" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000418</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000418" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000418</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7e1775e660067b5765d31150afc00030" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nasal_Ridge,Narrow-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7e1775e660067b5765d31150afc00030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
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Short nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854114</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003196</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003196</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=25661c4279536e7705f328dbb0964878" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nose,Short-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=25661c4279536e7705f328dbb0964878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
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Small nose <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249310005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249310005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426414&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426414</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003196</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003196</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=25661c4279536e7705f328dbb0964878" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nose,Short-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=25661c4279536e7705f328dbb0964878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
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Flaring nares <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3275431&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3275431</a>]</span><br /> -
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Anteverted nares <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/708670007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">708670007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840077&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840077</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=656ef0aca7742d97c5769f51f0dd56de" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nares,Anteverted-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=656ef0aca7742d97c5769f51f0dd56de" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
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Broad nasal tip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249327002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249327002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426429&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426429</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000455</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000455</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6ddac380d031baefd82dea5c5d13ca2a" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nasal_Tip,Broad-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6ddac380d031baefd82dea5c5d13ca2a" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Mouth </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Everted lower lip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/767502001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">767502001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853246</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000232" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000232</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000232" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000232</a>]</span><br /> -
|
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Open mouth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/262016004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">262016004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240379</a>, <a href="https://bioportal.bioontology.org/search?q=C4285242&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4285242</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000194" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000194</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000194" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000194</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> SKIN, NAILS, & HAIR </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Skin </em>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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- Large nevus (greater than 10 cm) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4011551&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4011551</a>]</span><br /> -
|
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Multiple nevi (up to hundreds) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4011552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4011552</a>]</span><br /> -
|
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Giant pigmented hairy nevus, often in lumbosacral distribution <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231513&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231513</a>]</span><br /> -
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Hair may not be present on the nevus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231512&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231512</a>]</span><br /> -
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Nevus spilus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398660000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398660000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/733523000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">733523000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0346099&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0346099</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025510</a>]</span><br /> -
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Spitz nevus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88082008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88082008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254811006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254811006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0206739&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0206739</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEOPLASIA </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Susceptibility to malignant melanoma <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3836884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3836884</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset at birth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836142&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836142</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003577" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003577</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003577" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003577</a>]</span><br /> -
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|
Relatives with multiple small congenital pigmented nevi<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by somatic mutation in the NRAS proto-oncogene, GTPase gene (NRAS, <a href="/entry/164790#0002">164790.0002</a>)<br /> -
|
|
Caused by somatic mutation in the HRas proto-oncogene, GTPase gene (HRAS, <a href="/entry/190020#0017">190020.0017</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<p>A number sign (#) is used with this entry because congenital melanocytic nevus syndrome (CMNS) is caused by somatic mutation in the NRAS gene (<a href="/entry/164790">164790</a>) on chromosome 1p13.</p><p>Two other forms of benign melanocytic proliferation, nevus spilus and Spitz nevus, are caused by somatic mutation in the HRAS gene (<a href="/entry/190020">190020</a>) on chromosome 11p15.</p>
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<p>Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, <a href="/entry/155600">155600</a>), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (<a href="/entry/249400">249400</a>), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by <a href="#11" class="mim-tip-reference" title="Kinsler, V. A., Chong, W. K., Aylett, S. E., Atherton, D. J. <strong>Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice.</strong> Brit. J. Derm. 159: 907-914, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18671780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18671780</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2008.08775.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18671780">Kinsler et al., 2008</a>; <a href="#13" class="mim-tip-reference" title="Kinsler, V., Shaw, A. C., Merks, J. H., Hennekam, R. C. <strong>The face in congenital melanocytic nevus syndrome.</strong> Am. J. Med. Genet. 158A: 1014-1019, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22438093</a>] [<a href="https://doi.org/10.1002/ajmg.a.34217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22438093">Kinsler et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22438093+18671780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by <a href="#15" class="mim-tip-reference" title="Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A. <strong>Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.</strong> JAMA Derm. 149: 1077-1080, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23884457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23884457</a>] [<a href="https://doi.org/10.1001/jamadermatol.2013.4745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23884457">Sarin et al., 2013</a>). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by <a href="#14" class="mim-tip-reference" title="Sarin, K. Y., McNiff, J. M., Kwok, S., Kim, J., Khavari, P. A. <strong>Activating HRAS mutation in nevus spilus. (Letter)</strong> J. Invest. Derm. 134: 1766-1768, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24390138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24390138</a>] [<a href="https://doi.org/10.1038/jid.2014.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24390138">Sarin et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24390138+23884457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Hecht, F., LaCanne, K. M., Carroll, D. B. <strong>Inheritance of giant pigmented hairy nevus of the scalp. (Letter)</strong> Am. J. Med. Genet. 9: 177-178, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258230</a>] [<a href="https://doi.org/10.1002/ajmg.1320090213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7258230">Hecht et al. (1981)</a> reported 2 first-cousin infants, a boy and a girl, who were born with giant pigmented hairy nevus (GPHN) of the scalp. The diameter of the nevi in each child approximated half of the scalp area, and the hair was dark in the center and of normal texture. Both infants showed normal development. Biopsies showed no evidence of malignancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7258230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Ho, N., Roig, C., Diadori, P. <strong>Epidermal nevi and localized cranial defects.</strong> Am. J. Med. Genet. 83: 187-190, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10096594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10096594</a>]" pmid="10096594">Ho et al. (1999)</a> reported a girl with sporadic occurrence of GPHN. At birth, she was noted to have a large patch of dark, coarse, thick hair over the right temporoparietal region of the scalp extending to the right occiput. There was also a separate small 1-cm hairy nevus adjacent to the front fontanel, and 2 epidermal sebaceous nevi on the right temple. CT scan showed an absence of the cranial bone underlying the large hairy nevus, with a size of about 7 x 6 cm. The bony edges of the cranial defect were irregular. The skull defect showed gradual spontaneous regression over the next 2 years, and the patient had normal development and no seizures. <a href="#10" class="mim-tip-reference" title="Ho, N., Roig, C., Diadori, P. <strong>Epidermal nevi and localized cranial defects.</strong> Am. J. Med. Genet. 83: 187-190, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10096594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10096594</a>]" pmid="10096594">Ho et al. (1999)</a> postulated a dysregulation of growth at the cellular and extracellular matrix level resulting from paracrine effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10096594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Stojanovic, S., Poljacki, M., Tasic, S., Preveden, R. <strong>Congenital giant pigmented hairy nevus--case report.</strong> Med. Pregl. 53: 305-308, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11089376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11089376</a>]" pmid="11089376">Stojanovic et al. (2000)</a> reported a 21-year-old woman with extensive GPHN covering 20% of her total body surface. The lesions covered the trunk, upper and lower extremities, and the face. They were congenital, but there had been no changes in color, size, or distribution. Family history was negative. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11089376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Foster, R. D., Williams, M. L., Barkovich, A. J., Hoffman, W. Y., Mathes, S. J., Frieden, I. J. <strong>Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.</strong> Plast. Reconstr. Surg. 107: 933-941, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11252085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11252085</a>] [<a href="https://doi.org/10.1097/00006534-200104010-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11252085">Foster et al. (2001)</a> reported follow-up of 46 patients with giant congenital melanocytic nevi, including 42 who underwent MR imaging. MRI abnormalities, consistent with neuromelanosis, were detected in 14 of 42 children, most of whom were under 12 months of age. <a href="#6" class="mim-tip-reference" title="Foster, R. D., Williams, M. L., Barkovich, A. J., Hoffman, W. Y., Mathes, S. J., Frieden, I. J. <strong>Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.</strong> Plast. Reconstr. Surg. 107: 933-941, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11252085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11252085</a>] [<a href="https://doi.org/10.1097/00006534-200104010-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11252085">Foster et al. (2001)</a> concluded that central nervous system melanosis is not a rare event in patients with giant congenital melanocytic nevi, but that most patients with abnormal findings remain asymptomatic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11252085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="de Wijn, R. S., Zaal, L. H., Hennekam, R. C. M., van der Horst, C. M. A. M. <strong>Familial clustering of giant congenital melanocytic nevi.</strong> J. Plast. Reconstr. Aesthet. Surg. 63: 906-913, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19464972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19464972</a>] [<a href="https://doi.org/10.1016/j.bjps.2009.02.090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19464972">De Wijn et al. (2010)</a> reported 2 unrelated families with recurrence of giant congenital melanocytic nevi. The first patient was a male infant with a typical giant melanocytic nevus (3 x 7 cm) with hairy patches on the occipital region of the head, covering about 1% total body surface area. His sister was born with a larger hairy melanocytic nevus on the back and buttocks, covering about 10% total body surface area. Both patients were otherwise healthy. In a second family, a girl was born with a hairy nevus covering about 30% total body surface area on the abdomen, back, buttocks, and upper legs. She also had 2 hypertrophic masses over the sacrum and mons pubis that were removed and found to contain pale myxoid matrix between nevus cells. Follow-up of this patient was uneventful. Family history revealed that the mother's niece had several large congenital melanocytic nevi covering about 11% body surface area and soft tissue hypotrophy of the affected right arm, as well as multiple satellite lesions all over her body, but no other abnormalities. These 2 familial cases were identified from a larger cohort of 120 patients, suggesting that familial occurrence is rare. <a href="#3" class="mim-tip-reference" title="de Wijn, R. S., Zaal, L. H., Hennekam, R. C. M., van der Horst, C. M. A. M. <strong>Familial clustering of giant congenital melanocytic nevi.</strong> J. Plast. Reconstr. Aesthet. Surg. 63: 906-913, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19464972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19464972</a>] [<a href="https://doi.org/10.1016/j.bjps.2009.02.090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19464972">De Wijn et al. (2010)</a> discussed possible involvement of the RAS/RAF/MAPK pathway as well as a disturbance in neural crest cell development due to a postzygotic mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19464972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Kinsler, V., Shaw, A. C., Merks, J. H., Hennekam, R. C. <strong>The face in congenital melanocytic nevus syndrome.</strong> Am. J. Med. Genet. 158A: 1014-1019, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22438093</a>] [<a href="https://doi.org/10.1002/ajmg.a.34217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22438093">Kinsler et al. (2012)</a> reviewed facial photographs of 95 Caucasian children with CMNS and concluded that there is a distinctive facial morphology. Most children (74%) in this series had at least 3 typical features, including wide or prominent forehead, apparent hypertelorism, eyebrow variants, periorbital fullness, small/short nose, narrow nasal ridge, broad nasal tip, broad or round face, full cheeks, prominent premaxilla, prominent or long philtrum, and everted lower lip. No association was found between the number of facial features and the severity of the cutaneous phenotype. The findings were consistent with the hypothesis that CMNS results from an abnormality of neural crest development, since the neural crest also contributes to facial development. <a href="#13" class="mim-tip-reference" title="Kinsler, V., Shaw, A. C., Merks, J. H., Hennekam, R. C. <strong>The face in congenital melanocytic nevus syndrome.</strong> Am. J. Med. Genet. 158A: 1014-1019, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22438093</a>] [<a href="https://doi.org/10.1002/ajmg.a.34217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22438093">Kinsler et al. (2012)</a> proposed the term 'congenital melanocytic nevus syndrome.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22438093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> studied tissue samples from 15 unrelated patients with congenital melanocytic nevi who ranged in age from 2 to 23 years. Three of the patients developed malignant melanoma and died at ages 2, 7, and 10 years. Two of those who died of melanoma had neurologic involvement. The lesions varied in size and number, but most patients had 50 to greater than 100 nevi, with the largest lesion greater than 60 cm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Spitz Nevus</em></strong></p><p>
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<a href="#15" class="mim-tip-reference" title="Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A. <strong>Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.</strong> JAMA Derm. 149: 1077-1080, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23884457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23884457</a>] [<a href="https://doi.org/10.1001/jamadermatol.2013.4745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23884457">Sarin et al. (2013)</a> studied a 25-year-old man who had a 4-year-history of pink papules arising in a large congenital pigmented tan patch on his left lower back. Examination showed a more than 20-cm diameter tan patch speckled with 1- to 2-mm hyperpigmented macules, characteristic of a nevus spilus, and containing 15 to 20 4- to 6-mm pink papules, characteristic of Spitz nevi. The patient was otherwise healthy, with no personal or family history of malignant melanoma. Histopathologic examination of 2 pink papules revealed symmetric, well-demarcated melanocytic proliferations consisting of spindle cell melanocytes with large vesicular nuclei splayed throughout the dermis, consistent with intradermal Spitz nevi. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23884457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Amir, J., Metzker, A., Nitzan, M. <strong>Giant pigmented nevus occurring in one identical twin.</strong> Arch. Derm. 118: 188-189, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7199895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7199895</a>]" pmid="7199895">Amir et al. (1982)</a> reported monozygotic twins who were discordant for giant pigmented nevus. At birth, the affected male infant was noted to have extensive areas of the skin over the trunk and thighs covered with a confluent, darkly pigmented nevus. He also had multiple smaller pigmented nevi on the entire body surface, and large tumor masses on the sacrum and scrotum. His twin brother had no detectable abnormalities. The findings argued against classic mendelian inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7199895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Congenital giant pigmented hairy nevus usually occurs sporadically, but familial occurrence has rarely been reported. By studying the families of 3 patients, <a href="#7" class="mim-tip-reference" title="Goodman, R. M., Caren, J., Ziprkowski, M., Padeh, B., Ziprkowski, L., Cohen, B. E. <strong>Genetic considerations in giant pigmented hairy naevus.</strong> Brit. J. Derm. 85: 150-157, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5571029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5571029</a>] [<a href="https://doi.org/10.1111/j.1365-2133.1971.tb07201.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5571029">Goodman et al. (1971)</a> found that each had relatives with multiple small pigmented nevi. The authors suggested autosomal dominant inheritance with variable expressivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5571029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Voigtlander, V., Jung, E. G. <strong>Giant pigmented hairy nevus in two siblings.</strong> Humangenetik 24: 79-84, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4426633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4426633</a>] [<a href="https://doi.org/10.1007/BF00281112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4426633">Voigtlander and Jung (1974)</a> observed affected sibs, and <a href="#8" class="mim-tip-reference" title="Hecht, F., LaCanne, K. M., Carroll, D. B. <strong>Inheritance of giant pigmented hairy nevus of the scalp. (Letter)</strong> Am. J. Med. Genet. 9: 177-178, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258230</a>] [<a href="https://doi.org/10.1002/ajmg.1320090213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7258230">Hecht et al. (1981)</a> reported affected first-cousins with an one instance of male-to-male transmission. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4426633+7258230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#13" class="mim-tip-reference" title="Kinsler, V., Shaw, A. C., Merks, J. H., Hennekam, R. C. <strong>The face in congenital melanocytic nevus syndrome.</strong> Am. J. Med. Genet. 158A: 1014-1019, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22438093</a>] [<a href="https://doi.org/10.1002/ajmg.a.34217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22438093">Kinsler et al. (2012)</a> proposed the following diagnostic criteria for congenital melanocytic nevus syndrome: (1) a CMN of greater than 5 cm projected adult size or more than 1 CMN of any size at birth, and (2) neurologic involvement, either clinical or radiologic, and/or 3 or more typical facial features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22438093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Kinsler, V. A., Chong, W. K., Aylett, S. E., Atherton, D. J. <strong>Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice.</strong> Brit. J. Derm. 159: 907-914, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18671780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18671780</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2008.08775.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18671780">Kinsler et al. (2008)</a> provided a protocol for the management of congenital melanocytic nevi based on the size of the largest CMN and the presence of satellite lesions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18671780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By cytogenetic analysis of a giant congenital pigmented nevus, <a href="#9" class="mim-tip-reference" title="Heimann, P., Ogur, G., De Busscher, C., Morandini, R., Libert, A., Vamos, E. <strong>Chromosomal findings in cultured melanocytes from a giant congenital nevus.</strong> Cancer Genet. Cytogenet. 68: 74-77, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8330286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8330286</a>] [<a href="https://doi.org/10.1016/0165-4608(93)90077-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8330286">Heimann et al. (1993)</a> found 74% normal mitoses, 22% polyploids, and 4% mitoses with chromosome rearrangements involving, in particular, chromosomes 1p, 12q, and 19p. Histology showed no signs of malignancy. Constitutional karyotype of the patient was normal. Microscopic examination of the nevus showed an infiltration of the dermis by regular nests or cords of nevus cells extending down to the reticular dermis and subcutaneous tissue. In the deeper part, the nevus cells displayed neuroid differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8330286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> identified somatic oncogenic missense mutations affecting codon 61 of the NRAS gene in affected cutaneous and neurologic tissues from 12 of 15 patients with CMNS and/or neurocutaneous melanosis. Affected skin samples from 10 of 13 patients carried a somatic heterozygous mutation, including 8 with Q61K (<a href="/entry/164790#0008">164790.0008</a>) and 2 with Q61R (<a href="/entry/164790#0002">164790.0002</a>). The same codon 61 mutation was found in each of the anatomically separate melanocytic nevi from the same patient. In addition, all 11 neurologic samples from 5 patients from whom neurologic tissue was available were positive for a somatic Q61K mutation; this included both melanocytic and nonmelanocytic tissue, such as a choroid plexus papilloma and meningioma. In patients with both neurologic and skin samples available, the same mutation was present in both affected tissues. None of the patients carried an NRAS mutation in the blood. Pre- and post-malignant skin tissue was available from a patient with malignant melanoma, which showed a progression from heterozygosity to homozygosity for the Q61K mutation with the onset of malignancy. Mutations at codon 61 in the NRAS gene affect the guanosine triphosphate-binding site and result in constitutive activation of NRAS. <a href="#12" class="mim-tip-reference" title="Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E. <strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong> J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>] [<a href="https://doi.org/10.1038/jid.2013.70" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23392294">Kinsler et al. (2013)</a> concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that these mutations may be lethal in the germline. Three of the original 15 patients with CMNS did not have NRAS mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Nevus Spilus and Spitz Nevus</em></strong></p><p>
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By exome sequencing in 2 Spitz nevi that arose within the nevus spilus of a 25-year-old man, <a href="#15" class="mim-tip-reference" title="Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A. <strong>Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.</strong> JAMA Derm. 149: 1077-1080, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23884457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23884457</a>] [<a href="https://doi.org/10.1001/jamadermatol.2013.4745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23884457">Sarin et al. (2013)</a> identified a missense mutation in the HRAS gene (G13R; <a href="/entry/190020#0017">190020.0017</a>) that was not found in the adjacent normal skin. Sanger sequencing revealed the same mutation in 2 more Spitz nevi from the patient. Copy number analysis confirmed amplification of HRAS in 2 of the nevi and polysomy in the melanocytes from a third Spitz nevus. No HRAS amplification was detected in adjacent fibroblasts or epidermal keratinocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23884457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Sarin, K. Y., McNiff, J. M., Kwok, S., Kim, J., Khavari, P. A. <strong>Activating HRAS mutation in nevus spilus. (Letter)</strong> J. Invest. Derm. 134: 1766-1768, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24390138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24390138</a>] [<a href="https://doi.org/10.1038/jid.2014.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24390138">Sarin et al. (2014)</a> analyzed nevi spili biopsy specimens from 8 unrelated patients and identified the G13R mutation in all, implicating the HRAS variant as the predominant causative mutation for nevi spili. Using laser-capture microdissection on 2 nevus spilus samples to isolate DNA from lentiginous melanocytes, junctional melanocytic nests, superficial dermis, and surrounding dermis, the authors demonstrated the presence of the G13R mutation in the melanocyte isolate but not in keratinocytes or dermal fibroblasts. <a href="#14" class="mim-tip-reference" title="Sarin, K. Y., McNiff, J. M., Kwok, S., Kim, J., Khavari, P. A. <strong>Activating HRAS mutation in nevus spilus. (Letter)</strong> J. Invest. Derm. 134: 1766-1768, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24390138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24390138</a>] [<a href="https://doi.org/10.1038/jid.2014.6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24390138">Sarin et al. (2014)</a> suggested that sporadic nevi spili result from a postzygotic mutation in the melanocytic lineage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24390138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large population-based study in South America, <a href="#2" class="mim-tip-reference" title="Castilla, E. E., da Graca Dutra, M., Orioli-Parreiras, I. M. <strong>Epidemiology of congenital pigmented naevi: I. Incidence rates and relative frequencies.</strong> Brit. J. Derm. 104: 307-315, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7213564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7213564</a>] [<a href="https://doi.org/10.1111/j.1365-2133.1981.tb00954.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7213564">Castilla et al. (1981)</a> estimated that the incidence of giant pigmented nevi greater than 10 cm is 1 in 20,455 live births. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7213564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The frequency of occurrence of congenital giant pigmented hairy nevus larger than 20 cm in diameter in pediatric patients has been estimated to be 1 in 4,150. Data on possible malignant transformation of these lesions into a melanoma vary from 6 to 12% (<a href="#17" class="mim-tip-reference" title="Stojanovic, S., Poljacki, M., Tasic, S., Preveden, R. <strong>Congenital giant pigmented hairy nevus--case report.</strong> Med. Pregl. 53: 305-308, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11089376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11089376</a>]" pmid="11089376">Stojanovic et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11089376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Although it is a common observation that nevi occur in families, probably with dominant transmission, the study by <a href="#4" class="mim-tip-reference" title="Denaro, S. J. <strong>The inheritance of nevi.</strong> J. Hered. 35: 215-218, 1944."None>Denaro (1944)</a> is one of the few that has examined the matter specifically. Multiple pigmented moles are a feature of one chromosomal aberration, the Turner syndrome, as pointed out by <a href="#16" class="mim-tip-reference" title="Sharpey-Schafer, E. P. <strong>Case of pterygo-nuchal infantilism (Turner's syndrome), with post-mortem findings.</strong> Lancet 238: 559-560, 1941. Note: Originally Volume II."None>Sharpey-Schafer (1941)</a> in the pre-chromosomal era. <a href="#5" class="mim-tip-reference" title="Estabrook, A. H. <strong>A family with birthmarks (nevus spilus) for five generations. (Abstract)</strong> Eugen. News 13: 90-92, 1928."None>Estabrook (1928)</a> reported affected persons in 5 generations of a family. (His term 'nevus spilus' comes from the Greek 'spilos' for 'spot.')</p>
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<strong>REFERENCES</strong>
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</span>
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|
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<p />
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</div>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Amir1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Amir, J., Metzker, A., Nitzan, M.
|
|
<strong>Giant pigmented nevus occurring in one identical twin.</strong>
|
|
Arch. Derm. 118: 188-189, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7199895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7199895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7199895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Castilla1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Castilla, E. E., da Graca Dutra, M., Orioli-Parreiras, I. M.
|
|
<strong>Epidemiology of congenital pigmented naevi: I. Incidence rates and relative frequencies.</strong>
|
|
Brit. J. Derm. 104: 307-315, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7213564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7213564</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7213564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2133.1981.tb00954.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="de Wijn2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Wijn, R. S., Zaal, L. H., Hennekam, R. C. M., van der Horst, C. M. A. M.
|
|
<strong>Familial clustering of giant congenital melanocytic nevi.</strong>
|
|
J. Plast. Reconstr. Aesthet. Surg. 63: 906-913, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19464972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19464972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19464972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.bjps.2009.02.090" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Denaro1944" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Denaro, S. J.
|
|
<strong>The inheritance of nevi.</strong>
|
|
J. Hered. 35: 215-218, 1944.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Estabrook1928" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Estabrook, A. H.
|
|
<strong>A family with birthmarks (nevus spilus) for five generations. (Abstract)</strong>
|
|
Eugen. News 13: 90-92, 1928.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Foster2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Foster, R. D., Williams, M. L., Barkovich, A. J., Hoffman, W. Y., Mathes, S. J., Frieden, I. J.
|
|
<strong>Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.</strong>
|
|
Plast. Reconstr. Surg. 107: 933-941, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11252085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11252085</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11252085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1097/00006534-200104010-00005" target="_blank">Full Text</a>]
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</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Goodman1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goodman, R. M., Caren, J., Ziprkowski, M., Padeh, B., Ziprkowski, L., Cohen, B. E.
|
|
<strong>Genetic considerations in giant pigmented hairy naevus.</strong>
|
|
Brit. J. Derm. 85: 150-157, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5571029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5571029</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5571029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2133.1971.tb07201.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Hecht1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hecht, F., LaCanne, K. M., Carroll, D. B.
|
|
<strong>Inheritance of giant pigmented hairy nevus of the scalp. (Letter)</strong>
|
|
Am. J. Med. Genet. 9: 177-178, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7258230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7258230</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7258230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1320090213" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Heimann1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heimann, P., Ogur, G., De Busscher, C., Morandini, R., Libert, A., Vamos, E.
|
|
<strong>Chromosomal findings in cultured melanocytes from a giant congenital nevus.</strong>
|
|
Cancer Genet. Cytogenet. 68: 74-77, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8330286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8330286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8330286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0165-4608(93)90077-y" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Ho1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ho, N., Roig, C., Diadori, P.
|
|
<strong>Epidermal nevi and localized cranial defects.</strong>
|
|
Am. J. Med. Genet. 83: 187-190, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10096594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10096594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10096594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
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|
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</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kinsler2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kinsler, V. A., Chong, W. K., Aylett, S. E., Atherton, D. J.
|
|
<strong>Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice.</strong>
|
|
Brit. J. Derm. 159: 907-914, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18671780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18671780</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18671780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2133.2008.08775.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kinsler2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E.
|
|
<strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong>
|
|
J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23392294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23392294</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23392294" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/jid.2013.70" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Kinsler2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kinsler, V., Shaw, A. C., Merks, J. H., Hennekam, R. C.
|
|
<strong>The face in congenital melanocytic nevus syndrome.</strong>
|
|
Am. J. Med. Genet. 158A: 1014-1019, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22438093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22438093</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22438093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.34217" target="_blank">Full Text</a>]
|
|
|
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|
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</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Sarin2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sarin, K. Y., McNiff, J. M., Kwok, S., Kim, J., Khavari, P. A.
|
|
<strong>Activating HRAS mutation in nevus spilus. (Letter)</strong>
|
|
J. Invest. Derm. 134: 1766-1768, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24390138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24390138</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24390138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/jid.2014.6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Sarin2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A.
|
|
<strong>Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.</strong>
|
|
JAMA Derm. 149: 1077-1080, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23884457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23884457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23884457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jamadermatol.2013.4745" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Sharpey-Schafer1941" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sharpey-Schafer, E. P.
|
|
<strong>Case of pterygo-nuchal infantilism (Turner's syndrome), with post-mortem findings.</strong>
|
|
Lancet 238: 559-560, 1941. Note: Originally Volume II.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Stojanovic2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stojanovic, S., Poljacki, M., Tasic, S., Preveden, R.
|
|
<strong>Congenital giant pigmented hairy nevus--case report.</strong>
|
|
Med. Pregl. 53: 305-308, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11089376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11089376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11089376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Voigtlander1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Voigtlander, V., Jung, E. G.
|
|
<strong>Giant pigmented hairy nevus in two siblings.</strong>
|
|
Humangenetik 24: 79-84, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4426633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4426633</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4426633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF00281112" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
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Marla J. F. O'Neill - updated : 6/16/2015
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Cassandra L. Kniffin - updated : 4/16/2014
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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carol : 09/19/2018
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carol : 06/18/2015<br>mcolton : 6/16/2015<br>carol : 4/18/2014<br>carol : 4/17/2014<br>ckniffin : 4/16/2014<br>carol : 4/6/2011<br>ckniffin : 4/4/2011<br>mimadm : 9/24/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/27/1989<br>marie : 3/25/1988<br>reenie : 6/4/1986
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<h3>
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<span class="mim-font">
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<strong>#</strong> 137550
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<h3>
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MELANOCYTIC NEVUS SYNDROME, CONGENITAL; CMNS
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<em>Alternative titles; symbols</em>
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GIANT PIGMENTED HAIRY NEVUS; GPHN<br />
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GIANT CONGENITAL PIGMENTED NEVUS<br />
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PIGMENTED MOLES
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<span class="mim-font">
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Other entities represented in this entry:
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NEVUS SPILUS, INCLUDED
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SPITZ NEVUS, INCLUDED
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<strong>SNOMEDCT:</strong> 10291008, 1260467009;
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<strong>ORPHA:</strong> 626;
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<strong>DO:</strong> 0111359;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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1p13.2
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<span class="mim-font">
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Melanocytic nevus syndrome, congenital, somatic
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<span class="mim-font">
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137550
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3
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NRAS
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164790
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11p15.5
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Spitz nevus or nevus spilus, somatic
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137550
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3
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HRAS
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<span class="mim-font">
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190020
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because congenital melanocytic nevus syndrome (CMNS) is caused by somatic mutation in the NRAS gene (164790) on chromosome 1p13.</p><p>Two other forms of benign melanocytic proliferation, nevus spilus and Spitz nevus, are caused by somatic mutation in the HRAS gene (190020) on chromosome 11p15.</p>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). </p><p>Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014). </p>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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<span class="mim-text-font">
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<p>Hecht et al. (1981) reported 2 first-cousin infants, a boy and a girl, who were born with giant pigmented hairy nevus (GPHN) of the scalp. The diameter of the nevi in each child approximated half of the scalp area, and the hair was dark in the center and of normal texture. Both infants showed normal development. Biopsies showed no evidence of malignancy. </p><p>Ho et al. (1999) reported a girl with sporadic occurrence of GPHN. At birth, she was noted to have a large patch of dark, coarse, thick hair over the right temporoparietal region of the scalp extending to the right occiput. There was also a separate small 1-cm hairy nevus adjacent to the front fontanel, and 2 epidermal sebaceous nevi on the right temple. CT scan showed an absence of the cranial bone underlying the large hairy nevus, with a size of about 7 x 6 cm. The bony edges of the cranial defect were irregular. The skull defect showed gradual spontaneous regression over the next 2 years, and the patient had normal development and no seizures. Ho et al. (1999) postulated a dysregulation of growth at the cellular and extracellular matrix level resulting from paracrine effects. </p><p>Stojanovic et al. (2000) reported a 21-year-old woman with extensive GPHN covering 20% of her total body surface. The lesions covered the trunk, upper and lower extremities, and the face. They were congenital, but there had been no changes in color, size, or distribution. Family history was negative. </p><p>Foster et al. (2001) reported follow-up of 46 patients with giant congenital melanocytic nevi, including 42 who underwent MR imaging. MRI abnormalities, consistent with neuromelanosis, were detected in 14 of 42 children, most of whom were under 12 months of age. Foster et al. (2001) concluded that central nervous system melanosis is not a rare event in patients with giant congenital melanocytic nevi, but that most patients with abnormal findings remain asymptomatic. </p><p>De Wijn et al. (2010) reported 2 unrelated families with recurrence of giant congenital melanocytic nevi. The first patient was a male infant with a typical giant melanocytic nevus (3 x 7 cm) with hairy patches on the occipital region of the head, covering about 1% total body surface area. His sister was born with a larger hairy melanocytic nevus on the back and buttocks, covering about 10% total body surface area. Both patients were otherwise healthy. In a second family, a girl was born with a hairy nevus covering about 30% total body surface area on the abdomen, back, buttocks, and upper legs. She also had 2 hypertrophic masses over the sacrum and mons pubis that were removed and found to contain pale myxoid matrix between nevus cells. Follow-up of this patient was uneventful. Family history revealed that the mother's niece had several large congenital melanocytic nevi covering about 11% body surface area and soft tissue hypotrophy of the affected right arm, as well as multiple satellite lesions all over her body, but no other abnormalities. These 2 familial cases were identified from a larger cohort of 120 patients, suggesting that familial occurrence is rare. De Wijn et al. (2010) discussed possible involvement of the RAS/RAF/MAPK pathway as well as a disturbance in neural crest cell development due to a postzygotic mutation. </p><p>Kinsler et al. (2012) reviewed facial photographs of 95 Caucasian children with CMNS and concluded that there is a distinctive facial morphology. Most children (74%) in this series had at least 3 typical features, including wide or prominent forehead, apparent hypertelorism, eyebrow variants, periorbital fullness, small/short nose, narrow nasal ridge, broad nasal tip, broad or round face, full cheeks, prominent premaxilla, prominent or long philtrum, and everted lower lip. No association was found between the number of facial features and the severity of the cutaneous phenotype. The findings were consistent with the hypothesis that CMNS results from an abnormality of neural crest development, since the neural crest also contributes to facial development. Kinsler et al. (2012) proposed the term 'congenital melanocytic nevus syndrome.' </p><p>Kinsler et al. (2013) studied tissue samples from 15 unrelated patients with congenital melanocytic nevi who ranged in age from 2 to 23 years. Three of the patients developed malignant melanoma and died at ages 2, 7, and 10 years. Two of those who died of melanoma had neurologic involvement. The lesions varied in size and number, but most patients had 50 to greater than 100 nevi, with the largest lesion greater than 60 cm. </p><p><strong><em>Spitz Nevus</em></strong></p><p>
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Sarin et al. (2013) studied a 25-year-old man who had a 4-year-history of pink papules arising in a large congenital pigmented tan patch on his left lower back. Examination showed a more than 20-cm diameter tan patch speckled with 1- to 2-mm hyperpigmented macules, characteristic of a nevus spilus, and containing 15 to 20 4- to 6-mm pink papules, characteristic of Spitz nevi. The patient was otherwise healthy, with no personal or family history of malignant melanoma. Histopathologic examination of 2 pink papules revealed symmetric, well-demarcated melanocytic proliferations consisting of spindle cell melanocytes with large vesicular nuclei splayed throughout the dermis, consistent with intradermal Spitz nevi. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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<span class="mim-text-font">
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<p>Amir et al. (1982) reported monozygotic twins who were discordant for giant pigmented nevus. At birth, the affected male infant was noted to have extensive areas of the skin over the trunk and thighs covered with a confluent, darkly pigmented nevus. He also had multiple smaller pigmented nevi on the entire body surface, and large tumor masses on the sacrum and scrotum. His twin brother had no detectable abnormalities. The findings argued against classic mendelian inheritance. </p><p>Congenital giant pigmented hairy nevus usually occurs sporadically, but familial occurrence has rarely been reported. By studying the families of 3 patients, Goodman et al. (1971) found that each had relatives with multiple small pigmented nevi. The authors suggested autosomal dominant inheritance with variable expressivity. </p><p>Voigtlander and Jung (1974) observed affected sibs, and Hecht et al. (1981) reported affected first-cousins with an one instance of male-to-male transmission. </p>
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<strong>Diagnosis</strong>
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<p>Kinsler et al. (2012) proposed the following diagnostic criteria for congenital melanocytic nevus syndrome: (1) a CMN of greater than 5 cm projected adult size or more than 1 CMN of any size at birth, and (2) neurologic involvement, either clinical or radiologic, and/or 3 or more typical facial features. </p>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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<p>Kinsler et al. (2008) provided a protocol for the management of congenital melanocytic nevi based on the size of the largest CMN and the presence of satellite lesions. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cytogenetics</strong>
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</span>
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<p>By cytogenetic analysis of a giant congenital pigmented nevus, Heimann et al. (1993) found 74% normal mitoses, 22% polyploids, and 4% mitoses with chromosome rearrangements involving, in particular, chromosomes 1p, 12q, and 19p. Histology showed no signs of malignancy. Constitutional karyotype of the patient was normal. Microscopic examination of the nevus showed an infiltration of the dermis by regular nests or cords of nevus cells extending down to the reticular dermis and subcutaneous tissue. In the deeper part, the nevus cells displayed neuroid differentiation. </p>
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<strong>Molecular Genetics</strong>
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<p>Kinsler et al. (2013) identified somatic oncogenic missense mutations affecting codon 61 of the NRAS gene in affected cutaneous and neurologic tissues from 12 of 15 patients with CMNS and/or neurocutaneous melanosis. Affected skin samples from 10 of 13 patients carried a somatic heterozygous mutation, including 8 with Q61K (164790.0008) and 2 with Q61R (164790.0002). The same codon 61 mutation was found in each of the anatomically separate melanocytic nevi from the same patient. In addition, all 11 neurologic samples from 5 patients from whom neurologic tissue was available were positive for a somatic Q61K mutation; this included both melanocytic and nonmelanocytic tissue, such as a choroid plexus papilloma and meningioma. In patients with both neurologic and skin samples available, the same mutation was present in both affected tissues. None of the patients carried an NRAS mutation in the blood. Pre- and post-malignant skin tissue was available from a patient with malignant melanoma, which showed a progression from heterozygosity to homozygosity for the Q61K mutation with the onset of malignancy. Mutations at codon 61 in the NRAS gene affect the guanosine triphosphate-binding site and result in constitutive activation of NRAS. Kinsler et al. (2013) concluded that multiple congenital melanocytic nevi and neuromelanosis, as well as nonmelanocytic CNS lesions, result from somatic mosaicism, and that the mutation probably occurs in a progenitor cell in the developing neural crest or neuroectoderm. The findings also suggested that these mutations may be lethal in the germline. Three of the original 15 patients with CMNS did not have NRAS mutations. </p><p><strong><em>Nevus Spilus and Spitz Nevus</em></strong></p><p>
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By exome sequencing in 2 Spitz nevi that arose within the nevus spilus of a 25-year-old man, Sarin et al. (2013) identified a missense mutation in the HRAS gene (G13R; 190020.0017) that was not found in the adjacent normal skin. Sanger sequencing revealed the same mutation in 2 more Spitz nevi from the patient. Copy number analysis confirmed amplification of HRAS in 2 of the nevi and polysomy in the melanocytes from a third Spitz nevus. No HRAS amplification was detected in adjacent fibroblasts or epidermal keratinocytes. </p><p>Sarin et al. (2014) analyzed nevi spili biopsy specimens from 8 unrelated patients and identified the G13R mutation in all, implicating the HRAS variant as the predominant causative mutation for nevi spili. Using laser-capture microdissection on 2 nevus spilus samples to isolate DNA from lentiginous melanocytes, junctional melanocytic nests, superficial dermis, and surrounding dermis, the authors demonstrated the presence of the G13R mutation in the melanocyte isolate but not in keratinocytes or dermal fibroblasts. Sarin et al. (2014) suggested that sporadic nevi spili result from a postzygotic mutation in the melanocytic lineage. </p>
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<p>In a large population-based study in South America, Castilla et al. (1981) estimated that the incidence of giant pigmented nevi greater than 10 cm is 1 in 20,455 live births. </p><p>The frequency of occurrence of congenital giant pigmented hairy nevus larger than 20 cm in diameter in pediatric patients has been estimated to be 1 in 4,150. Data on possible malignant transformation of these lesions into a melanoma vary from 6 to 12% (Stojanovic et al., 2000). </p>
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<p>Although it is a common observation that nevi occur in families, probably with dominant transmission, the study by Denaro (1944) is one of the few that has examined the matter specifically. Multiple pigmented moles are a feature of one chromosomal aberration, the Turner syndrome, as pointed out by Sharpey-Schafer (1941) in the pre-chromosomal era. Estabrook (1928) reported affected persons in 5 generations of a family. (His term 'nevus spilus' comes from the Greek 'spilos' for 'spot.')</p>
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<strong>REFERENCES</strong>
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Amir, J., Metzker, A., Nitzan, M.
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<strong>Giant pigmented nevus occurring in one identical twin.</strong>
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Arch. Derm. 118: 188-189, 1982.
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[PubMed: 7199895]
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Castilla, E. E., da Graca Dutra, M., Orioli-Parreiras, I. M.
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<strong>Epidemiology of congenital pigmented naevi: I. Incidence rates and relative frequencies.</strong>
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Brit. J. Derm. 104: 307-315, 1981.
|
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[PubMed: 7213564]
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[Full Text: https://doi.org/10.1111/j.1365-2133.1981.tb00954.x]
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de Wijn, R. S., Zaal, L. H., Hennekam, R. C. M., van der Horst, C. M. A. M.
|
|
<strong>Familial clustering of giant congenital melanocytic nevi.</strong>
|
|
J. Plast. Reconstr. Aesthet. Surg. 63: 906-913, 2010.
|
|
|
|
|
|
[PubMed: 19464972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bjps.2009.02.090]
|
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</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
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Denaro, S. J.
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<strong>The inheritance of nevi.</strong>
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J. Hered. 35: 215-218, 1944.
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<p class="mim-text-font">
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Estabrook, A. H.
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<strong>A family with birthmarks (nevus spilus) for five generations. (Abstract)</strong>
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Eugen. News 13: 90-92, 1928.
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</p>
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</li>
|
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<li>
|
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|
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Foster, R. D., Williams, M. L., Barkovich, A. J., Hoffman, W. Y., Mathes, S. J., Frieden, I. J.
|
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<strong>Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.</strong>
|
|
Plast. Reconstr. Surg. 107: 933-941, 2001.
|
|
|
|
|
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[PubMed: 11252085]
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|
|
|
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[Full Text: https://doi.org/10.1097/00006534-200104010-00005]
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</li>
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Goodman, R. M., Caren, J., Ziprkowski, M., Padeh, B., Ziprkowski, L., Cohen, B. E.
|
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<strong>Genetic considerations in giant pigmented hairy naevus.</strong>
|
|
Brit. J. Derm. 85: 150-157, 1971.
|
|
|
|
|
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[PubMed: 5571029]
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|
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|
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[Full Text: https://doi.org/10.1111/j.1365-2133.1971.tb07201.x]
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</li>
|
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|
|
<li>
|
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<p class="mim-text-font">
|
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Hecht, F., LaCanne, K. M., Carroll, D. B.
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<strong>Inheritance of giant pigmented hairy nevus of the scalp. (Letter)</strong>
|
|
Am. J. Med. Genet. 9: 177-178, 1981.
|
|
|
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|
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[PubMed: 7258230]
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[Full Text: https://doi.org/10.1002/ajmg.1320090213]
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<li>
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Heimann, P., Ogur, G., De Busscher, C., Morandini, R., Libert, A., Vamos, E.
|
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<strong>Chromosomal findings in cultured melanocytes from a giant congenital nevus.</strong>
|
|
Cancer Genet. Cytogenet. 68: 74-77, 1993.
|
|
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|
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[PubMed: 8330286]
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[Full Text: https://doi.org/10.1016/0165-4608(93)90077-y]
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Ho, N., Roig, C., Diadori, P.
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<strong>Epidermal nevi and localized cranial defects.</strong>
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Am. J. Med. Genet. 83: 187-190, 1999.
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[PubMed: 10096594]
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Kinsler, V. A., Chong, W. K., Aylett, S. E., Atherton, D. J.
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<strong>Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice.</strong>
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Brit. J. Derm. 159: 907-914, 2008.
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[PubMed: 18671780]
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[Full Text: https://doi.org/10.1111/j.1365-2133.2008.08775.x]
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Kinsler, V. A., Thomas, A. C., Ishida, M., Bulstrode, N. W., Loughlin, S., Hing, S., Chalker, J., McKenzie, K., Abu-Amero, S., Slater, O., Chanudet, E., Palmer, R., Morrogh, D., Stanier, P., Healy, E., Sebire, N. J., Moore, G. E.
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<strong>Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.</strong>
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J. Invest. Derm. 133: 2229-2236, 2013. Note: Erratum: J. Invest. Derm. 136: 2326 only, 2016.
|
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|
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[PubMed: 23392294]
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[Full Text: https://doi.org/10.1038/jid.2013.70]
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<p class="mim-text-font">
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Kinsler, V., Shaw, A. C., Merks, J. H., Hennekam, R. C.
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<strong>The face in congenital melanocytic nevus syndrome.</strong>
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Am. J. Med. Genet. 158A: 1014-1019, 2012.
|
|
|
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|
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[PubMed: 22438093]
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[Full Text: https://doi.org/10.1002/ajmg.a.34217]
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Sarin, K. Y., McNiff, J. M., Kwok, S., Kim, J., Khavari, P. A.
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<strong>Activating HRAS mutation in nevus spilus. (Letter)</strong>
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J. Invest. Derm. 134: 1766-1768, 2014.
|
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[PubMed: 24390138]
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[Full Text: https://doi.org/10.1038/jid.2014.6]
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Sarin, K. Y., Sun, B. K., Bangs, C. D., Cherry, A., Swetter, S. M., Kim, J., Khavari, P. A.
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<strong>Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.</strong>
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JAMA Derm. 149: 1077-1080, 2013.
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[PubMed: 23884457]
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[Full Text: https://doi.org/10.1001/jamadermatol.2013.4745]
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</li>
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Sharpey-Schafer, E. P.
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<strong>Case of pterygo-nuchal infantilism (Turner's syndrome), with post-mortem findings.</strong>
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Lancet 238: 559-560, 1941. Note: Originally Volume II.
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Stojanovic, S., Poljacki, M., Tasic, S., Preveden, R.
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<strong>Congenital giant pigmented hairy nevus--case report.</strong>
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Med. Pregl. 53: 305-308, 2000.
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[PubMed: 11089376]
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Voigtlander, V., Jung, E. G.
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<strong>Giant pigmented hairy nevus in two siblings.</strong>
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Humangenetik 24: 79-84, 1974.
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[PubMed: 4426633]
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[Full Text: https://doi.org/10.1007/BF00281112]
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<p>
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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